Transarterial Embolization in Maxillofacial Intractable Potentially Life-Threatening Hemorrhage.

PURPOSE: Although transarterial embolization (TAE) of vascular lesions with embolizing agents through angiographic catheters has been used for more than 45 years, reports of life-threatening maxillofacial bleeding are relatively rare and have not been updated. The authors review treatment modalities, present their experience of the past 21 years, and suggest a comprehensive algorithm and guidelines for the use of TAE in the treatment of intractable life-threatening maxillofacial hemorrhage. MATERIALS AND METHODS: This article describes 28 patients treated with TAE for severe bleeding that did not respond to conservative therapies. Of these, 13 had uncontrolled epistaxis, 9 were oncologic patients, 4 were postsurgical patients, and 2 were trauma patients. RESULTS: Details of patients' medical history, failed conservative therapy administered before TAE, imaging results, and blood vessels involved are presented, as are the TAE procedures and materials used, outcome, and complications. All these are discussed in relation to the available updated literature. All 9 oncologic patients (100%) had been treated with chemotherapy before the uncontrolled bleeding, and 7 also had radiotherapy administered to the maxillofacial region. Continuous anticoagulant therapy also seemed to predict such bleeding episodes. TAE resolved the bleeding in all 28 cases and rapidly in 90% of cases. Only in 3 oncologic cases did continued bleeding require 3 to 4 consecutive TAE sessions and combinations of embolizing agents. CONCLUSIONS: The reported high rate of success could be the result of careful techniques, appropriate preoperative imaging, highly professional personnel, and intraoperative and perioperative treatments.

The TSPO Ligands MGV-1 and 2-Cl-MGV-1 Differentially Inhibit the Cigarette Smoke-Induced Cytotoxicity to H1299 Lung Cancer Cells.

TSPO is involved in cigarette smoke (CS)-induced cellular toxicity, which may result in oral and pulmonary diseases and lung cancer. H1299 lung cancer cells were exposed directly to CS. The H1299 cells were pretreated with our TSPO ligands MGV-1 and 2-Cl-MGV-1 (Ki = 825 nM for both) at a concentration of 25 µM 24 h prior to CS exposure. Cell death and apoptotic markers were measured, in addition to TSPO expression levels, ATP synthase activity, generation of reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (ΔΨm), cAMP and LDH levels. Pretreatment with MGV-1 and 2-Cl-MGV-1 (25 µM), 24 h prior to CS exposure, differentially attenuated the CS-induced cellular insult as well as cell death in H1299 lung cancer cells. These protective effects included prevention of ATP synthase reversal, ROS generation, depolarization of the mitochondrial membrane and elevation in LDH. The preventive efficacy of 2-Cl-MGV-1 was superior to that achieved by MGV-1. Both ligands did not prevent the elevation in cAMP. These findings may indicate a mild protective effect of these TSPO ligands in CS-related pulmonary and keratinocyte cellular pathology.

p27 and salivary cancer.

This study examined p27 expression in a cohort of salivary malignancies (n = 74) for a prolonged period (20 years). Reduction of p27 expression was found to be a most powerful predictor for poor survival and more so when the tumor concurrently expressed high levels of p53, TUNEL and heparanase markers, dramatically dropping the patient survival probability to 0! While no patient whose tumor-staining profile included: p27 > 50%, p53 = 0, TUNEL = 0 and heparanase = 0, died of the disease during the 20-year follow up, the median of survival of the group with p27 0, TUNEL > 0 and heparanase > 0 was only 39 months. The survival probabilities of these two groups at 5 years were 100 and 50%, respectively, and at 20 years they were 100 and 0%, respectively (P = 0.05). Significant p27 reduction also resulted in significantly larger tumor size (T value), higher spread of neck metastasis and extra capsular spread and in more advanced disease (higher stage). Significant correlation rates were found between age and poor survival, age and reduced p27 expression, and reduced p27 expression and other general co-existing malignancies, indicating p27 reduction as part of a general phenomenon-age related mutagenesis. Significantly more extensive therapy applied to patients with salivary reduced-p27 tumors could not prevent the rise in mortality rate, questioning the justification for extensive therapy which is naturally accompanied by higher morbidity. Additional therapeutic tools for fighting salivary cancer, possibly based on the new understanding of the p27, p53, TUNEL and heparanase carcinogenic network, are necessary.

The expression and prognostic significance of Cks1 in salivary cancer.

Cks1 is an essential factor in facilitating Skp2-dependent degradation of p27, but its role in salivary malignancies is unknown. Expression of cyclin-dependent kinase subunit 1 (Cks1) was examined in 64 salivary malignancies, compared with p27, S-phase kinase protein 2 (Skp2), Ki-67, p53, and TDT-mediated dutp-biotin nick end labeling (TUNEL) expression, and with THE patient's clinical and pathological parameters. Cks1 expression was markedly increased in 30 patients (47%) and strongly correlated with increased expression of Skp2, Ki-67, p53, and TUNEL, but inversely with p27 levels. High expression of Cks1 WAS strongly associated with lymph node metastases and poor prognosis and survival. Cks1 alterations may have a significant biological role in the pathogenesis of salivary cancer.

Foreign body granulomas after injection of Bio-alcamid for lip augmentation.

Bio-alcamid is one of the newest agents on the market for soft tissue augmentation. Seven studies were documented in the medical literature that examined the safety of Bio-alcamid (Polymekon, Brindisy, Italy); all reported no cases of tissue migration, foreign body granulomas, allergenicity, or interference with the control of cell proliferation. On 2 separate occasions, a woman who had recently undergone lip augmentation presented at our hospital with submucosal nodules of the lip. Histologic examination revealed multiple foreign body-type granulomas composed of giant cells, epithelioid cells, and chronic inflammation of the lip. Efforts to produce a cosmetic material that fulfills all the criteria as an "ideal" agent has not yet been found because all injectable foreign agents have the potential to induce adverse reactions. Caution must be exercised in all cases and the risks explained to the patient before its use.

Ki67 and salivary cancer.

We examined Ki67 expression in salivary malignancies of 75 patients with a follow-up period of up to 20 years. Correlations between enhanced Ki67 and enhanced p53 and TUNEL and heparanase staining levels were significant. Median survival for reduced-stained-tumor patients (< or = 5%) was 163 months, dropping significantly to 39 months (p = 0.0005) for enhanced stained tumors (> 5%); 5 year survival probability was 93% and 33%, respectively, 45% and 16%, respectively, (p = 0.0005) at 20 years. Significant correlation between poor survival and concurrently altered expression rates of Ki67 and p53, p27 Skp2, TUNEL and heparanase in the salivary malignancies indicates a biological role in salivary cancer pathogenesis.

TUNEL as a tumor marker of tongue cancer.

Squamous cell carcinoma (SCC) of the tongue has an increasing incidence, a high morbidity rate and a 50% 5-year mortality rate. We analyzed the rate of apoptosis using TDT-mediated dUTP-biotin nick end-labeling (TUNEL), p53 and heparanase in 73 patients with tongue cancer by immonohistochemistry, and tested data for correlation with survival, tumor size, grade and metastasis. TUNEL staining was strong in 54% of the tumors; the remainder lacked staining, as did all healthy control tissues. Significant correlations were found between TUNEL staining level and p53 expression rates (p=0.016) and between TUNEL and heparanase (p=0.039). Moreover, while the cumulative 5-year survival probability for tumors not stained for TUNEL and p53 was 63%, but dropped to 34% with TUNEL staining; for lack of TUNEL and heparanase (=0), 5-year survival rate was 50%, while staining presence (>0) reduced survival to 34%. TUNEL joins other biomarkers in indicating prognosis of understanding pathogenesis of tongue cancer.

Salivary analysis and antioxidants in cleft lip and palate children.

OBJECTIVE: To investigate the sialometry, sialochemistry and antioxidants in cleft patients prior to alveolar closure procedures. DESIGN: Saliva was collected from 21 children with unilateral and bilateral cleft lip and palate (UCLP and BCLP) with overt oronasal alveolar communication and with recurrent licking of fluids and soft diet complaints (the study group) and in 22 normal individuals (the control group). Salivary flow rate was measured, and calcium (Ca), phosphate (P), magnesium (Mg), total protein, albumin, amylase, lactate dehydrogenase (LDH), and secretory IgA were analysed. Salivary total antioxidant status (TAS), peroxidase activity, superoxide dismutase (SOD) activity, uric acid (UA), was also determined. RESULTS: The sialometry and sialochemistry analyses did not reveal significant difference between the two groups. Salivary median uric acid concentration was 6-fold lower in the cleft group (p<0.05). The median total antioxidant status (TAS) of the cleft group however, was significantly higher by 58% (p<0.005) than that of the control group. Median SOD activity was also higher in the cleft group, by 42%, though these differences did not reach statistical significance. CONCLUSIONS: Our findings suggest that the oral biology system of cleft patients in their prealveolar closure stage does not differ significantly from normal controls. Low UA found in the saliva of cleft patients may suggest that some genetic alteration of the UA transport occurs simultaneously when cleft lip and palate occur. TAS reduction may also reveal an increased oxidative stress burden in the oral cavities of cleft children which has never been shown before.

Relationship of flow rate, uric acid, peroxidase, and superoxide dismutase activity levels with complications in diabetic patients: can saliva be used to diagnose diabetes?

Can salivary free radicals and antioxidant parameters be useful in general diagnosis and evaluation of diabetes mellitus Type II (DM)? Serum and salivary redox state of 40 diabetes mellitus patients were examined and compared with 20 controls. The involvement of salivary gland in diabetes mellitus has been suggested based on salivary flow rate and compositional alterations. In addition, the redox state of saliva of diabetes mellitus patients is different than that of normoglycemic control human subjects. This observation unveils the opportunity to use noninvasive saliva-based diagnostics for diabetes mellitus patients.

A comprehensive salivary analysis for oral cancer diagnosis.

PURPOSE: This study utilized comprehensive salivary analysis to evaluate biochemical and immunological parameters in the saliva of oral squamous cell carcinoma (OSCC) patients. METHODS: Whole saliva was collected from 25 otherwise healthy OSCC patients and compared to 25 healthy, age- and gender-matched individuals. All OSCC lesions were located at the lateral aspect of the mobile tongue. The salivary parameters analyzed included: sodium (Na), potassium (K), calcium (Ca), inorganic phosphate (P), magnesium (Mg), total protein (TP), albumin (Alb), lactate dehydrogenase (LDH), amylase (Amy), total immunoglobulin G (IgG), secretory immunoglobulin A (Sec. IgA), epidermal growth factor, insulin growth factor I (IGF-I) and metalloproteinases MMP-2 and MMP-9. RESULTS: In cancer patients, salivary median total protein concentration was significantly higher by 26% (P = 0.01), as were concentrations of Na, Ca, P and Mg by 14% (P = 0.05), 59% (P = 0.05), 39% (P = 0.08) and 28% (P = 0.12), respectively. Amy and K concentrations were lower by 25% (P = 0.12) and 15% (P = 0.03), respectively. Alb was 108% higher (P = 0.0007), as were salivary LDH (88%, P = 0.002) and total IgG (125%, P = 0.01), while Sec. IgA was lower by 45% (P = 0.001). Concentrations of IGF, MMP-2 and MMP-9 were significantly higher by 117% (P = 0.03), 75% (P = 0.0003) and 35% (P = 0.05), respectively. CONCLUSIONS: Comprehensive salivary analysis revealed an overall altered salivary composition in OSCC, indicating a compromised oral environment in these patients and suggesting salivary analysis as a new diagnostic tool for oral cancer. Local therapeutic agents can be easily applied to the oral mucosa, altering its "bathing medium"-the saliva.

Age-related changes in salivary antioxidant profile: possible implications for oral cancer.

Oral cancer's much higher prevalence among older people may be due to an age-related reduction in protective salivary antioxidant mechanisms and/or an age-related increase in the magnitude of oral carcinogen attack, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), causing DNA aberrations. This study found a significantly reduced total value of salivary antioxidant capacity in elderly persons (as measured by overall antioxidant capacity [ImAnOx] assay), (46% of healthy individuals, p =.004), increased oxidative stress (86% increase in carbonyl concentrations--indicators of enhanced ROS attack, p =.001), and increased salivary concentrations and total values of RNS (7-fold and 3-fold higher respectively, p =.001), all contributing to increased DNA oxidation of oral epithelial cells. Salivary oxidative stress-related changes in the intimately related saliva and oral epithelium compounded with higher viscosity of saliva may explain the higher prevalence of oral cancer in the elderly population. Administration of local therapeutic agents (i.e., antioxidants) to the oral cavity should be considered.

Effects of diabetes mellitus, chronic renal failure and hemodialysis on serum and salivary antioxidant status.

AIM: To analyze various oxidative stress parameters in the saliva and serum of patients with chronic renal failure (CRF) and/or diabetes mellitus (DM), and to compare them in dialytic vs. pre-dialytic patients. METHOD: 50 consenting patients were divided into five subgroups of patients: severe CRF (dialytic) without DM, severe CRF (dialytic) with DM, mild CRF (pre-dialytic) without DM, mild CRF (pre-dialytic) with DM, and with DM but without CRF (controls). Uric acid (UA), peroxidase and total antioxidant status (TAS) were studied in both saliva and serum; superoxide dismutase (SOD) was evaluated only in saliva. Both saliva collection and serum harvesting were done simultaneously. RESULTS: In severe-CRF patients without DM, median TAS, UA and SOD levels decreased following dialysis (54, 85, 48%, respectively), and peroxidase levels increased slightly (9%). In severe-CRF patients with DM, median TAS and SOD levels increased following dialysis (33 and 54%, respectively) while median UA and peroxidase levels decreased (68 and 10%, respectively). CONCLUSIONS: DM, CRF and hemodialysis were found to increase the oxidative stress burden in both serum and saliva. Therefore, antioxidant assessment may be used to monitor baseline oxidative status in these situations though larger randomized studies are in order.

Oxidative stress indices in COPD--Broncho-alveolar lavage and salivary analysis.

OBJECTIVE: It has been suggested that oxidative stress plays a role in the pathogenesis of chronic obstructive pulmonary disease (COPD), though this role has yet to be fully elucidated. The purpose of this study was to further evaluate this role as concomitantly expressed in the saliva and broncho-alveolar lavage (BAL/'lavage'). DESIGN: Forty consenting patients (mean age 62+/-13-year-old), with/without COPD and/or smoking habit, participated in the study. The following antioxidant profile was examined both in saliva and lavage of the patients: total antioxidant status (TAS), uric acid (UA), peroxidase and super oxide dismutase (SOD). Total protein (TP) and albumin (Alb) were also evaluated in both saliva and lavage while amylase was measured only in saliva. RESULTS: Increase of TAS (by 100%) and of SOD activity levels (by 60%) in the lavage of COPD patients indicated oxidative stress. The salivary UA in COPD patients was 125% higher (p = 0.05) while the peroxidase was 20% higher. Another novel finding was that levels of salivary antioxidants in smoking versus non-smoking COPD patients were lower by 25-48% (for all four: TAS, UA, peroxidase and SOD) while the albumin was significantly reduced by 60% (p = 0.018). CONCLUSION: Oxidative-stress-related changes demonstrated both in the lavage and saliva of the COPD and/or smoking patient indicate cumulative effects of both, also emphasizing the pathogenetic role of free radicals in COPD. Salivary analysis, which is less invasive and much easier to perform as compared with lavage analysis, is suggested as a new and effective diagnostic tool in COPD patients.

Salivary beta2-microglobulin analysis in chronic kidney disease and hemodialyzed patients.

BACKGROUND: Beta2-microglobulin (beta2m) is a major component in dialysis-related amyloidosis, a disabling disease affecting long-term dialysis patients. METHODS: Beta2m and other components were analyzed in saliva and serum from 53 individuals in 4 subgroups: healthy normal controls, diabetes mellitus (DM), chronic kidney disease (CKD) and hemodialysis (HD) patients. RESULTS: Median salivary and mean serum beta2m concentrations were 78% higher in both saliva (p = 0.048) and serum (p = 0.047) in DM patients; 118% (p = 0.016) and 907% (p = 0.007) higher, respectively, in CKD patients, and 328% (p = 0.0001) and 2,710% (p = 0.001) higher, respectively, in HD patients, compared with healthy controls. The correlation analysis between salivary and serum beta2m concentrations showed a low correlation rate in HD patients (r = -0.18), but was rather high in CKD patients (r = 0.50). CONCLUSIONS: Salivary analysis of beta2m is a reliable method for evaluating serum beta2m levels in CKD patients, and may help predict the potential for development of CKD-induced amyloidosis.

Salivary oxidative stress in children during acute asthmatic attack and during remission.

BACKGROUND: Patients with asthma generate an increased amount of reactive oxygen species from peripheral blood cells, which may contribute to its pathogenesis. Saliva analysis is non-invasive and friendly to children. We undertook this study to analyze the salivary oxidative profile and composition in children with asthma during attack and remission, and to compare them with the levels of salivary antioxidants of healthy control children. METHODS: School age (range 6-18 years) children referred to the emergency room for acute asthma were included. Clinical score was assessed, spirometry performed, and saliva samples were collected and analyzed. All measurements were repeated during remission of asthma attack (2-4 weeks after attack). Salivary analysis was performed blindly during asthma attack and the results were compared to those obtained during remission, and to those of the control group. RESULTS: Statistically significant decreases in levels of salivary peroxidase enzyme activity were observed in asthmatic children during attack compared with healthy controls, with partial recovery during remission of attack. Similarly decreased levels of calcium concentrations were observed in asthmatic children, accompanied by increased phosphate levels. CONCLUSIONS: Children with acute asthma attacks exhibit a decrease in the activity of the most important salivary antioxidant enzyme-peroxidase, which is accompanied by other salivary composition alterations. Hence, acute asthma is manifested by salivary changes. This implies systemic oxidative stress in asthma, which may be reflected in salivary analysis.

Free radicals related effects and antioxidants in saliva and serum of adolescents with Type 1 diabetes mellitus.

OBJECTIVE: The purpose of the current study was to analyze both serum and salivary composition and oxidative stress markers in Type 1 diabetes mellitus (DM) patients. DESIGN: Twenty consenting patients with DM but otherwise healthy patients aged 13-19 years and 12 healthy controls, matching in age and gender (Group 1), participated in the study. The patients were divided according to those who had controlled diabetes mellitus (Group 2) or uncontrolled diabetes mellitus (Group 3). All were analyzed for saliva composition and antioxidants. Saliva was also analyzed for its levels of superoxide dismutase (SOD) and amylase activity, total IgA and total IgG concentrations and potassium, phosphorus, magnesium and calcium electrolyte concentrations. RESULTS: A significant correlation was found between the severity of the DM/HbA1c values and the increase in both salivary and/or serum antioxidants (peroxidase, SOD and TAS), and the various TCL parameters (H1, H3, pre-incubation and oxygenation-potential). CONCLUSIONS: The two most important findings of the current study relate to the role of oxidative stress in the pathogenesis of Type 1 diabetes mellitus and to the involvement of salivary glands in the disease. The profound effects of DM on salivary antioxidant parameters may be also of great importance in respect to the diagnosis and evaluation of the disease. The correlation between altered salivary parameters and the severity of the disease may indicate that evaluation of the salivary status of DM patients as part of the assessment of their disease activity and severity is warranted.

Association between regional idiopathic neuropathy and salivary involvement as the possible mechanism for oral sensory complaints.

UNLABELLED: The idiopathic sensorial disturbances of burning mouth syndrome (BMS), taste disturbances (dysgeusia), and dry mouth (xerostomia) have recently been recognized as one entity and given the generic name of oral sensorial complaints (OSC). However, not all patients with OSC complain of all three disturbances, and the underlying mechanism of OSC has not yet been elucidated. This study sought to determine whether OSC was associated with the alteration of oral sensory perception, salivary profile and/or personality traits. It examined 35 patients with OSC and 19 controls. Sensory perception was assessed by Quantitative Sensory Testing (QST) applied to the tongue, including thresholds for thermal sensations and pain, and the magnitude estimation of tonic suprathreshold heat pain stimuli. The salivary profile included flow rate and compositional analysis. Personality traits were examined by both state and trait anxiety and somatization scoring. Results showed significantly elevated thermal sensory thresholds and decreased pain scores for tonic heat pain. In addition, there was an increased level of somatization in the OSC group as compared to the control group (15.1 +/- 1.5 vs. 6.6 +/- 2.1, respectively; P = .003). Concomitantly, altered salivary composition (elevated Na, K, Cl, Ca, IgA, and amylase concentrations)-but not salivary flow rate reduction-was observed in those patients despite their complaints of oral dryness. All parameters were similar among the patients with OSC regardless of their type of complaint. Linear regression analysis revealed that an elevated warm sensory threshold was associated with higher levels of salivary K and Cl concentrations in the patients with OSC. These findings may be attributed to a regional small fiber idiopathic neuropathy affecting oral sensation and salivary secretion in OSC. Alternatively, a primary idiopathic salivary dysfunction might cause sensory neural dysfunction at the receptor level by changing the oral cavity milieu. PERSPECTIVE: Based on the salivary, psychophysical, and personality traits analysis currently presented, as well as on the available literature, we hypothesize that a comprehensive mechanism for OSC is based on a regional neuropathy, which is expressed by complaints of BMS, taste disturbances, and/or xerostomia. All are clearly distinguishable from similar conditions with established organic/therapeutic-related etiologies.

Oropharyngeal cancer pathogenesis: ubiquitin proteolytic, apoptotic and epidermal growth factor related pathways act in concert--first report.

The current study was carried out to examine the clinical characteristics and survival-probability rates of 51 patients treated for oral (tongue) cancer and to correlate it with various tumor markers. The clinical data and survival probability rates were correlated with the immunohistological analysis of p27, Skp2, p53, Bcl-2, TUNEL (apoptotic rate) and c-erbB-2 markers. The 5-year survival-probability correlated with staging, grading and base of tongue location. An inverse relation between the expression of p27 and Skp2, p27 and grading, and a direct relation between Skp2 and grading were demonstrated. Concomitantly, significant correlations between low p27, high Skp2 and high TUNEL (apoptotic rate) expressions and between low p27 and high c-erbB-2 (Her2) expressions in the cancer lesions were demonstrated. The accumulated data may be employed in the future for a better understanding of the biology behind oral cancer and for developing better means of detection and treatment.

Relationships between age, drugs, oral sensorial complaints and salivary profile.

The aim of this study was to investigate the relationships between oral sensorial complaints (OSCs) and salivary flow rate, composition and drug consumption of subjects aged 18-90 years. The results were correlated with both drug consumption and OSCs. Only individuals who were free of conditions that are already known to cause OSCs were included in the study. The three most significant observations were as follows: (1) elderly people have significantly reduced and altered salivary secretion compared with younger people. While specific concentrations increased, the total values of most salivary components decreased in the elderly; (2) 50% of the elderly population have OSCs regarding taste, burning mouth syndrome or xerostomia; and (3) OSCs were more prevalent in elderly people who use drugs than in those who do not. In conclusion, a reduction in salivary function and altered composition are age related. A compensatory capacity that prevents OSCs appears to exist in elderly patients who do not use drugs, but drugs were found to have an extensive effect on OSCs. The finding that the total amounts of salivary components and not only the salivary flow rate were reduced in elderly people is of great clinical relevance, since such a reduction is expected to be reflected in compromising various salivary functions.

Carbonyl levels and survival rates in oral cancer cells exposed to cigarette smoke.

BACKGROUND: Cigarette smoke (CS) is the main inducer of oral cancer, increasing prevalence 4-7 times. MATERIALS AND METHODS: We examined SCC-25 and SCC-15 suitability for studying CS effects on oral cancer cells, measuring carbonyl levels for free radical-mediated CS effect on survival and time/CS dependence. RESULTS: Protein oxidation increased significantly during CS exposure. At all time points, carbonyl levels increased six-fold (p<0.001) in both cell lines. Cell viability decrease was time-dependent. Longer CS exposure led to higher cell mortality. At 120 min, SCC-25 cell survival reduction was 43.7%, (p<0.01). Propidium iodide (PI) assay results matched the Trypan blue assay showing a time-dependent cell viability decrease following CS exposure. At 120 min, cell survival reduction was 37% (p<0.05). CONCLUSION: Cell death is mediated by CS free radicals with pathological process occurring first. Oral cancer cell models SCC-25 and SCC-15 are suitable for studying CS-induced free radical-related damage, potentially leading to the pathogenesis of oral cancer.